Long-term toxicity of ortho-toluenesulfonamide and sodium saccharin in the rat

In a two-generation lifetime feeding study, 50 male and 50 female weanling Sprague-Dawley rats were included in each of the following dietary treatment groups: control; 2.5 mg ortho-toluenesulfonamide (o-TS, more than 99.9% pure)/kg/day; 25 mg o-TS/kg/day; 250 mg o-TS/kg/day; 250 mg o-TS/kg/day with 1% NH₄Cl in the drinking water: or 5% sodium saccharin, which contained no detectable amount of o-TS. After 3 months on test, the F₀ rats were bred and 50 pups of each sex, from every group, were weaned onto the parental diets which both generations received for their lifetime. Rats from both generations fed diets providing 250 mg o-TS/kg with 1.0% NH₄Cl in the drinking water or containing 5% sodium saccharin had decreased growth rates, but only the former two had lowered feed consumption. There were no treatment-related effects upon reproduction, longevity, or hematological parameters. The animals were free of the bladder parasite Trichosomoides crassicauda. A few animals developed grossly visible bladder and kidney stones but the incidence of these was not treatment related. The incidence of bladder tumours in male rats fed the 5% saccharin diet was significantly increased in both generations compared to their respective control groups. An evaluation of individual feed consumption data for animals fed saccharin-containing diets did not reveal any statistical difference between the amount of feed consumed by animals which had bladder tumors and those that did not. The incidence of bladder tumors in the o-TS-treated groups and in the female rats fed the 5% saccharin diet was not significantly different from that in control animals.